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A new off-line model of exhaled nitric oxide (eNO) measurement for preschool children
S214 Abstracts
Applicability of Interrupter Resistance Measurements in Evaluation of Exercise-Induced Bronchospasm D. Song, H. Kim, J. Choung; Department of Pediatrics, Korea University Medical college hospital, Seoul, REPUBLIC OF KOREA. RATIONALE: The interrupter technique is a non-invasive method for measuring air flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in young children. The aim of this study was to evaluate applicability interrupter resistance(Rint) measurements in assessment of exercise-induced bronchospasm. METHODS: 45 children aged 5 to 12 years with mild to moderate asthma were tested by exercise challenge consisting of free outdoor running for 6 min. Rint, peak expiratory flow rate(PEFR), forced expiratory volume in one second(FEV1) were measured before and 10 min after exercise. In addition, PEFR was measured at 5, 15, and 20 min after exercise. The repeatability of Rint was assessed, and Rint responses to exercise challenge were compared with other method. RESULTS: The repeatability coefficient for baseline Rint was 0.06 kPaL1s. The exercise challenge was positive in 16(35%) of 45 children; a fall of 15% or more in PEFR associated with wheezing or cough after excercise was considered positive. Rint identified 13 positive cases with a sensitivity of 81% and specificity of 93% at the cutoff level of a 15% rise in resistance after excercise. CONCLUSIONS: The results of exercise challenge test using Rint were comparable with the current standardized method to detect exerciseinduced bronchospasm. The interrupter resistance measurement provides a useful alternative for assessment of exercise-induced bronchospasm in young and uncooperative children.
850
A New Off-Line Model of Exhaled Nitric Oxide (eNO) Measurement for Preschool Children A. Thatayatikom1,2, L. B. Bacharier1,2, P. Lee1, K. L. Hodgdon1,2, G. R. Bloomberg1,2, R. C. Strunk1,2; 1Allergy and Pulmonary Medicine, St. Louis Children’s Hospital, St. Louis, MO, 2Washington University School of Medicine, St. Louis, MO. RATIONALE: eNO measurement is an attractive test to assess airway inflammation in young children since it is noninvasive and easily obtained without requiring a special maneuver. The purpose of this study was to test a newly designed off-line eNO collection model in preschool children. METHODS: An off-line eNO collection model based on the ATS/ERS guidelines was designed to incorporate a partitioned face mask and a 5cmH2O CPAP valve. 2 or 3 samples of 5 exhaled breaths were collected for each child and FeNO analyzed using the NIOX off-line system. 40 children 12-59 months old presenting to an allergy clinic for a scheduled visit were evaluated. Subjects had ≥2 wheezing episodes, no acute respiratory illness or other chronic lung disease, and no oral corticosteroid therapy within 2 weeks. RESULTS: 11 subjects (age 23-54 months) with excessive intra-individual coefficients of variation (CV) between 2 FeNO samples (CV>20%), and 5 subjects (age 12-50 months) with poor technique (crying, laughing, irregular breathing) were excluded from analysis. 24 subjects with intraindividual CV≤20% were analyzed. 8 subjects (group1) were receiving no controllers, 8 (group 2) received low dose inhaled corticosteroid (ICS), and 8 (group 3) received moderate dose ICS. Median FeNO for all 3 groups was 11.0 ppb (interquartile range 6.17-17.6ppb, minimum 3.7ppb, maximum 49.5ppb). FeNO was lowest in group 3 (median FeNO group13 = 19.4, 15.0, 6.5ppb respectively, p=0.03, Kruskal-Wallis test). CONCLUSIONS: This offline tidal breathing eNO model may be a practical model for preschool children; however, further studies to control intraindividual variability are needed. (NIH/NHLBI 5-U10-HL64287-03 funded) Funding: NIH/NHLBI
851
TUESDAY
Exhaled Breath Condensates Nitrite Levels Inversely Correlate With pH A. H. Liu1,2, W. J. Morgan3,2, A. M. Schiltz4,2, R. L. James5,2, S. J. Szefler4,2, H. Mitchell5,2, W. W. Busse6,2; 1Pediatrics, National Jewish Med-
852
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
ical and Research Center, Denver, CO, 2Inner City Asthma Consortium, Madison, WI, 3Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ, 4Pediatrics, National Jewish Medical Research Center, Denver, CO, 5Rho, Inc., Chapel Hill, NC, 6Medicine, University of Wisconsin Hospital and Clinics, Madison, WI. RATIONALE: Nitrite is a product of oxidant stress and has been detected in airway fluids of asthmatics. We hypothesized that nitrite levels in exhaled breath condensate (EBC) could be reproducibly measured and might correlate with other airways-specific biomarkers associated with childhood asthma. METHODS: In a pilot study of the NIH/NIAID-funded Inner City Asthma Consortium, two separate EBC samples from children ages 6 to 18 years with mild to moderately severe asthma (n=52) or without asthma (n=10) were collected, using the R-Tube (Respiratory Research; Charlottesville, VA). EBC nitrite concentrations were measured via Griess Reagent System (Promega; Madison, WI). EBC pH was measured on Argon de-gassed EBC samples. Exhaled nitric oxide (eNO) was measured via NIOX system (Aerocrine, Inc; NY, NY). RESULTS: For nitrite measures, the median intra-sample coefficient of variation was 1.50% (range 0.01-29.11%). Between the first and second EBC samples, EBC nitrite did not differ (nitrite median 0.586 mcM vs. 0.555 mcM, p=0.78). The correlation between the first and second samples was r=0.42, p=0.0007. EBC nitrite was negatively correlated with EBC pH (r=-0.35, p=0.006). EBC nitrite did not correlate with eNO (p=0.32). CONCLUSIONS: Elevated EBC nitrite may serve as a distinct and useful indicator of oxidant stress in the airways of asthmatic children. Funding: NIH/NIAID N01-AI-25496 Effect of Tobacco Smoke Exposure on Exhaled Nitric Oxide Levels in Healthy African Americans D. W. Hauswirth1, C. A. Fernandez2, S. Mervin-Blake2, K. B. Patch2, K. E. Morgan2, M. C. Levesque2, J. S. Sundy3; 1Pediatrics, Allergy and Immunology, Duke University, Durham, NC, 2Medicine, Rheumatology and Immunology, Duke University, Durham, NC, 3Medicine, Rheumatology and Allergy, Duke University, Durham, NC. RATIONALE: To determine the relationship of tobacco smoke exposure, as measured by serum cotinine concentration, to exhaled nitric oxide (ENO) levels in a healthy African American population. METHODS: Healthy African American men and women between 18 and 40 years old were recruited for a study of genetic correlates of ENO levels. Participants were self-reported non-smokers, and reported no medication use; history of chronic illness; asthma or atopy. ENO was measured by chemiluminescence and taken as an average of three readings. Serum cotinine levels were measured by ELISA. RESULTS: 564 subjects were evaluated. Serum cotinine concentrations ranged from 0.0 to 909.7 ng/mL. Despite self-reported non-smoking, 10% of subjects had cotinine concentrations indicative of regular cigarette smoking (≥25 ng/mL), and 11% had cotinine concentrations indicative of intermittent active or passive exposure to tobacco smoke (1-25 ng/mL). The geometric mean ENO level in smokers (cotinine ≥25 ng/mL, n=56) [13.08 ppb; 95% CI 10.46-16.34] was significantly lower than the mean ENO level in non-smokers (cotinine = 0 ng/mL, n=334) [21.52 ppb; 95%CI 19.95-23.21] (p<0.001). The geometric mean ENO levels in subjects with intermediate exposure (cotinine 1-25 ng/mL) was not significantly different that that of non-smokers. Furthermore, ENO levels among smokers was significantly and inversely correlated with increased serum cotinine concentration of ≥ 25 ng/mL (r=-0.351, p=0.008). CONCLUSIONS: There is a direct inverse correlation between tobacco smoke exposure and ENO levels in healthy African Americans. These data indicate that assesment of cotinine levels is important in ruling out significant tobacco smoke exposure when interpreting ENO measurements. Funding: Sandler Program for Asthma Research; ES012496; MO1RR-30
853
Applicability of Interrupter Resistance Measurements in Evaluation of Exercise-Induced Bronchospasm D. Song, H. Kim, J. Choung; Department of Pediatrics, Korea University Medical college hospital, Seoul, REPUBLIC OF KOREA. RATIONALE: The interrupter technique is a non-invasive method for measuring air flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in young children. The aim of this study was to evaluate applicability interrupter resistance(Rint) measurements in assessment of exercise-induced bronchospasm. METHODS: 45 children aged 5 to 12 years with mild to moderate asthma were tested by exercise challenge consisting of free outdoor running for 6 min. Rint, peak expiratory flow rate(PEFR), forced expiratory volume in one second(FEV1) were measured before and 10 min after exercise. In addition, PEFR was measured at 5, 15, and 20 min after exercise. The repeatability of Rint was assessed, and Rint responses to exercise challenge were compared with other method. RESULTS: The repeatability coefficient for baseline Rint was 0.06 kPaL1s. The exercise challenge was positive in 16(35%) of 45 children; a fall of 15% or more in PEFR associated with wheezing or cough after excercise was considered positive. Rint identified 13 positive cases with a sensitivity of 81% and specificity of 93% at the cutoff level of a 15% rise in resistance after excercise. CONCLUSIONS: The results of exercise challenge test using Rint were comparable with the current standardized method to detect exerciseinduced bronchospasm. The interrupter resistance measurement provides a useful alternative for assessment of exercise-induced bronchospasm in young and uncooperative children.
850
A New Off-Line Model of Exhaled Nitric Oxide (eNO) Measurement for Preschool Children A. Thatayatikom1,2, L. B. Bacharier1,2, P. Lee1, K. L. Hodgdon1,2, G. R. Bloomberg1,2, R. C. Strunk1,2; 1Allergy and Pulmonary Medicine, St. Louis Children’s Hospital, St. Louis, MO, 2Washington University School of Medicine, St. Louis, MO. RATIONALE: eNO measurement is an attractive test to assess airway inflammation in young children since it is noninvasive and easily obtained without requiring a special maneuver. The purpose of this study was to test a newly designed off-line eNO collection model in preschool children. METHODS: An off-line eNO collection model based on the ATS/ERS guidelines was designed to incorporate a partitioned face mask and a 5cmH2O CPAP valve. 2 or 3 samples of 5 exhaled breaths were collected for each child and FeNO analyzed using the NIOX off-line system. 40 children 12-59 months old presenting to an allergy clinic for a scheduled visit were evaluated. Subjects had ≥2 wheezing episodes, no acute respiratory illness or other chronic lung disease, and no oral corticosteroid therapy within 2 weeks. RESULTS: 11 subjects (age 23-54 months) with excessive intra-individual coefficients of variation (CV) between 2 FeNO samples (CV>20%), and 5 subjects (age 12-50 months) with poor technique (crying, laughing, irregular breathing) were excluded from analysis. 24 subjects with intraindividual CV≤20% were analyzed. 8 subjects (group1) were receiving no controllers, 8 (group 2) received low dose inhaled corticosteroid (ICS), and 8 (group 3) received moderate dose ICS. Median FeNO for all 3 groups was 11.0 ppb (interquartile range 6.17-17.6ppb, minimum 3.7ppb, maximum 49.5ppb). FeNO was lowest in group 3 (median FeNO group13 = 19.4, 15.0, 6.5ppb respectively, p=0.03, Kruskal-Wallis test). CONCLUSIONS: This offline tidal breathing eNO model may be a practical model for preschool children; however, further studies to control intraindividual variability are needed. (NIH/NHLBI 5-U10-HL64287-03 funded) Funding: NIH/NHLBI
851
TUESDAY
Exhaled Breath Condensates Nitrite Levels Inversely Correlate With pH A. H. Liu1,2, W. J. Morgan3,2, A. M. Schiltz4,2, R. L. James5,2, S. J. Szefler4,2, H. Mitchell5,2, W. W. Busse6,2; 1Pediatrics, National Jewish Med-
852
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
ical and Research Center, Denver, CO, 2Inner City Asthma Consortium, Madison, WI, 3Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ, 4Pediatrics, National Jewish Medical Research Center, Denver, CO, 5Rho, Inc., Chapel Hill, NC, 6Medicine, University of Wisconsin Hospital and Clinics, Madison, WI. RATIONALE: Nitrite is a product of oxidant stress and has been detected in airway fluids of asthmatics. We hypothesized that nitrite levels in exhaled breath condensate (EBC) could be reproducibly measured and might correlate with other airways-specific biomarkers associated with childhood asthma. METHODS: In a pilot study of the NIH/NIAID-funded Inner City Asthma Consortium, two separate EBC samples from children ages 6 to 18 years with mild to moderately severe asthma (n=52) or without asthma (n=10) were collected, using the R-Tube (Respiratory Research; Charlottesville, VA). EBC nitrite concentrations were measured via Griess Reagent System (Promega; Madison, WI). EBC pH was measured on Argon de-gassed EBC samples. Exhaled nitric oxide (eNO) was measured via NIOX system (Aerocrine, Inc; NY, NY). RESULTS: For nitrite measures, the median intra-sample coefficient of variation was 1.50% (range 0.01-29.11%). Between the first and second EBC samples, EBC nitrite did not differ (nitrite median 0.586 mcM vs. 0.555 mcM, p=0.78). The correlation between the first and second samples was r=0.42, p=0.0007. EBC nitrite was negatively correlated with EBC pH (r=-0.35, p=0.006). EBC nitrite did not correlate with eNO (p=0.32). CONCLUSIONS: Elevated EBC nitrite may serve as a distinct and useful indicator of oxidant stress in the airways of asthmatic children. Funding: NIH/NIAID N01-AI-25496 Effect of Tobacco Smoke Exposure on Exhaled Nitric Oxide Levels in Healthy African Americans D. W. Hauswirth1, C. A. Fernandez2, S. Mervin-Blake2, K. B. Patch2, K. E. Morgan2, M. C. Levesque2, J. S. Sundy3; 1Pediatrics, Allergy and Immunology, Duke University, Durham, NC, 2Medicine, Rheumatology and Immunology, Duke University, Durham, NC, 3Medicine, Rheumatology and Allergy, Duke University, Durham, NC. RATIONALE: To determine the relationship of tobacco smoke exposure, as measured by serum cotinine concentration, to exhaled nitric oxide (ENO) levels in a healthy African American population. METHODS: Healthy African American men and women between 18 and 40 years old were recruited for a study of genetic correlates of ENO levels. Participants were self-reported non-smokers, and reported no medication use; history of chronic illness; asthma or atopy. ENO was measured by chemiluminescence and taken as an average of three readings. Serum cotinine levels were measured by ELISA. RESULTS: 564 subjects were evaluated. Serum cotinine concentrations ranged from 0.0 to 909.7 ng/mL. Despite self-reported non-smoking, 10% of subjects had cotinine concentrations indicative of regular cigarette smoking (≥25 ng/mL), and 11% had cotinine concentrations indicative of intermittent active or passive exposure to tobacco smoke (1-25 ng/mL). The geometric mean ENO level in smokers (cotinine ≥25 ng/mL, n=56) [13.08 ppb; 95% CI 10.46-16.34] was significantly lower than the mean ENO level in non-smokers (cotinine = 0 ng/mL, n=334) [21.52 ppb; 95%CI 19.95-23.21] (p<0.001). The geometric mean ENO levels in subjects with intermediate exposure (cotinine 1-25 ng/mL) was not significantly different that that of non-smokers. Furthermore, ENO levels among smokers was significantly and inversely correlated with increased serum cotinine concentration of ≥ 25 ng/mL (r=-0.351, p=0.008). CONCLUSIONS: There is a direct inverse correlation between tobacco smoke exposure and ENO levels in healthy African Americans. These data indicate that assesment of cotinine levels is important in ruling out significant tobacco smoke exposure when interpreting ENO measurements. Funding: Sandler Program for Asthma Research; ES012496; MO1RR-30
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